Research will be performed to determine the mechanism of formate toxicity. Formate produces marked ocular toxicity characterized by optic disc edema and a necrosis of the optic nerve. Studies will be performed in order to determine the effect of formate on energy producing systems in various tissues and especially in the retina and optic nerve of rats and monkeys. Studies will be performed in order to determine whether formate is toxic to the rat and whether ocular toxicity can be discerned in this species. The folate metabolic pathway will be evaluated in rat and monkey in order to determine its role in the metabolism of formate. Studies on various enzymatic steps are underway to determine the key steps in the regulation of tetrahydrofolate formation, as well as the regulation of formate oxidation to carbon dioxide.